Background:In this study,we analyzed the potential active components,related crucial targets and possible signaling pathway mechanisms of Alpiniae Oxyphyllae Fructus and Saposhnikoviae Radix(AOF-SR)herb pairs in the t...Background:In this study,we analyzed the potential active components,related crucial targets and possible signaling pathway mechanisms of Alpiniae Oxyphyllae Fructus and Saposhnikoviae Radix(AOF-SR)herb pairs in the treatment of diabetic kidney disease(DKD)using network pharmacology and verification experiments.Methods:The active compounds and potential targets of AOF-SR were derived from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,The Encyclopedia of Traditional Chinese Medicine,and PubChem databases,and the potential therapeutic targets of DKD were derived from the OMIM,Drugbank,and DisGeNET databases.The“compounds-diseases-targets”network was constructed using Cytoscape 3.6.0.ClusterMaker functionality in Cytoscape is being used to screen important targets for AOF-SR treatment of DKD.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of important targets were performed using DAVID database.In addition,according to the predicted results of network pharmacology,HK-2 cells were used to construct DKD model for verification experiment.HK-2 cells were divided into control group,high glucose(HG)group and AOF-SR(HG+AOF-SR)group to detect survival rate and expression of key proteins in NF-κB and PI3K/Akt signaling pathways.Results:A total of 38 compounds were selected from AOF-SR,of which 23 were Alpiniae Oxyphyllae Fructus and 15 were Saposhnikoviae Radix.Through enrichment analysis of 82 important targets,88 signaling pathways were identified;some of these pathways,such as the NF-κB,PI3K-Akt,IL-17,and JAK/STAT signaling pathways,regulate the pathological process of DKD.In verification experiment,the HK-2 cells survival rate was higher in the HG+AOF-SR group than in the HG group(P<0.05).Moreover,western blotting results showed that the expression levels of NF-κB,p-PI3K,and p-Akt in HG+AOF-SR group were significantly lower than those in HG group(P<0.05).Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of AOF-SR treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by AOF-SR.展开更多
[Objectives]To explore the protective effect of Alpinia zerumbet(Pers.)Burttet Smith ethanol extraction(YSJ)on gastric ulcers.[Methods]The ethanol-induced gastric ulcer model was generated by male Kunming mice.The mic...[Objectives]To explore the protective effect of Alpinia zerumbet(Pers.)Burttet Smith ethanol extraction(YSJ)on gastric ulcers.[Methods]The ethanol-induced gastric ulcer model was generated by male Kunming mice.The mice were divided into six groups,including control,model(GU),positive omeprazole enteric-coated capsules(18 mg/kg),YSJ low(1.17 g/kg),medium(2.34 g/kg)and high(4.68 g/kg)dose groups.To observe the state of gastric tissues,hematoxylin and eosin(H&E)staining was applied and immunohistochemistry(IHC)was used to evaluate the expression of nuclear factor kappa-B p65(NF-κB p65),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α),and Cyclooxygenase-2(COX-2)in gastric tissues.The ulcer index,biochemical parameters,and inflammatory proteins were evaluated.In vitro,GES-1 cells were induced by anhydrous ethanol to found gastric ulcer model.The groups were the same as in vivo experiment.Cytotoxicity was tested by MTT and IL-1β,TNF-α,and IL-6 were detected by Elisa assays.[Results]The injuries of gastric tissue in the model group were unambiguously observed and improved after YSJ treatment.The levels of interleukin 1 beta(IL-1β),interleukin 6(IL-6),interleukin 8(IL-8),and TNF-αin serum and tissues were decreased(P<0.05 or 0.01),whereas interleukin 4(IL-4)and prostaglandin E 2(PGE 2)were increased after treatment with YSJ(P<0.05 or 0.01).The levels of IL-1β,IL-6,TNF-α,and IL-8 were decreased in YSJ groups,while IL-4 and PGE 2 presented the opposite trend.The protein expression of p-NF-κB,NF-κB,p-IκBα,IκBα,and TNF-αwas inhibited after treatment with YSJ(P<0.05 or 0.01).[Conclusions]These results demonstrate that YSJ alleviates the occurrence and development of gastric ulcers via inhibiting inflammation.展开更多
基金the National Natural Science Foundation of China(grant No.82160897,82205087)Hainan Provincial Natural Science Foundation of China(grant No.820RC635)+1 种基金Scientific Research Foundation of Hainan Medical University(grant No.HYPY201924,HYPY2020037)Hainan Medical University 2020 National Innovation and Entrepreneurship Program for College Students(grant No.202011810006).
文摘Background:In this study,we analyzed the potential active components,related crucial targets and possible signaling pathway mechanisms of Alpiniae Oxyphyllae Fructus and Saposhnikoviae Radix(AOF-SR)herb pairs in the treatment of diabetic kidney disease(DKD)using network pharmacology and verification experiments.Methods:The active compounds and potential targets of AOF-SR were derived from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,The Encyclopedia of Traditional Chinese Medicine,and PubChem databases,and the potential therapeutic targets of DKD were derived from the OMIM,Drugbank,and DisGeNET databases.The“compounds-diseases-targets”network was constructed using Cytoscape 3.6.0.ClusterMaker functionality in Cytoscape is being used to screen important targets for AOF-SR treatment of DKD.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of important targets were performed using DAVID database.In addition,according to the predicted results of network pharmacology,HK-2 cells were used to construct DKD model for verification experiment.HK-2 cells were divided into control group,high glucose(HG)group and AOF-SR(HG+AOF-SR)group to detect survival rate and expression of key proteins in NF-κB and PI3K/Akt signaling pathways.Results:A total of 38 compounds were selected from AOF-SR,of which 23 were Alpiniae Oxyphyllae Fructus and 15 were Saposhnikoviae Radix.Through enrichment analysis of 82 important targets,88 signaling pathways were identified;some of these pathways,such as the NF-κB,PI3K-Akt,IL-17,and JAK/STAT signaling pathways,regulate the pathological process of DKD.In verification experiment,the HK-2 cells survival rate was higher in the HG+AOF-SR group than in the HG group(P<0.05).Moreover,western blotting results showed that the expression levels of NF-κB,p-PI3K,and p-Akt in HG+AOF-SR group were significantly lower than those in HG group(P<0.05).Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of AOF-SR treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by AOF-SR.
基金Supported by Guizhou Provincial Basic Research Program(Natural Science)(ZK[2022]-492&[2020]1Y045)the National Natural Science Foundation of China(82260767).
文摘[Objectives]To explore the protective effect of Alpinia zerumbet(Pers.)Burttet Smith ethanol extraction(YSJ)on gastric ulcers.[Methods]The ethanol-induced gastric ulcer model was generated by male Kunming mice.The mice were divided into six groups,including control,model(GU),positive omeprazole enteric-coated capsules(18 mg/kg),YSJ low(1.17 g/kg),medium(2.34 g/kg)and high(4.68 g/kg)dose groups.To observe the state of gastric tissues,hematoxylin and eosin(H&E)staining was applied and immunohistochemistry(IHC)was used to evaluate the expression of nuclear factor kappa-B p65(NF-κB p65),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α),and Cyclooxygenase-2(COX-2)in gastric tissues.The ulcer index,biochemical parameters,and inflammatory proteins were evaluated.In vitro,GES-1 cells were induced by anhydrous ethanol to found gastric ulcer model.The groups were the same as in vivo experiment.Cytotoxicity was tested by MTT and IL-1β,TNF-α,and IL-6 were detected by Elisa assays.[Results]The injuries of gastric tissue in the model group were unambiguously observed and improved after YSJ treatment.The levels of interleukin 1 beta(IL-1β),interleukin 6(IL-6),interleukin 8(IL-8),and TNF-αin serum and tissues were decreased(P<0.05 or 0.01),whereas interleukin 4(IL-4)and prostaglandin E 2(PGE 2)were increased after treatment with YSJ(P<0.05 or 0.01).The levels of IL-1β,IL-6,TNF-α,and IL-8 were decreased in YSJ groups,while IL-4 and PGE 2 presented the opposite trend.The protein expression of p-NF-κB,NF-κB,p-IκBα,IκBα,and TNF-αwas inhibited after treatment with YSJ(P<0.05 or 0.01).[Conclusions]These results demonstrate that YSJ alleviates the occurrence and development of gastric ulcers via inhibiting inflammation.
